Development of the skin and its derivatives

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1 Development of the skin and its derivatives Resources: Larsen s Human Embryology Chapter 7 The Developing Human: Clinically Oriented Embryology Dr Annemiek Beverdam School of Medical Sciences, UNSW Wallace Wurth Building Room 234

2 Lecture overview Skin function and anatomy Skin origins Development of the overlying epidermis Development of epidermal appendages: Hair follicles Glands Nails Teeth Development of melanocytes Development of the Dermis Resources: Larsen s Human Embryology Chapter 7 The Developing Human: Clinically Oriented Embryology Dr Annemiek Beverdam School of Medical Sciences, UNSW Wallace Wurth Building Room 234

3 Skin Function and Anatomy Largest organ of our body Protects inner body from outside world (pathogens, water, sun) Thermoregulation Diverse: thick vs thin skin, scalp skin vs face skin, etc Consists of: - Overlying epidermis - Epidermal appendages: - Hair follicles, - Glands: sebaceous, sweat, apocrine, mammary - Nails - Teeth - Melanocytes - (Merkel Cells - Langerhans cells) - Dermis - Hypodermis

4 Skin origins Trilaminar embryo Ectoderm (Neural crest) brain, spinal cord, eyes, peripheral nervous system epidermis of skin and associated structures, melanocytes, cranial connective tissues (dermis) Mesoderm musculo-skeletal system, limbs connective tissue of skin and organs urogenital system, heart, blood cells Endoderm epithelial linings of gastrointestinal and respiratory tracts

5 Ectoderm Overlying epidermis, epidermal appendages, nerve endings

6 Neural Crest Melanocytes + Cranial Connective Tissue Melanocytes Cranial Connective Tissue

7 Mesoderm Dermis, Hypodermis Somitic mesoderm (yellow): dermomyotome -> dorsal dermis Somatic lateral plate mesoderm (purple) -> ventral dermis

8 Embryonic development: Page 342 S.F. Gilbert Developmental Biology 5th edition

9 Epidermal development Surface ectoderm Skin/Interfollicular epidermis: stratified squamous epithelium Appendages: Hair follicles Glands (sebaceous, sweat, apocrine, mammary, lacrimal, salivary) Nails Teeth

10 Development of Skin/interfollicular epidermis (IFE) Week 4 Week 11 Onset of stratification Week 24

11 Development of Skin/interfollicular epidermis (IFE) Periderm formation: 4 weeks Periderm Basement membrane Basal layer

12 Development of Skin/interfollicular epidermis (IFE) Stratification Week 11: intermediate layer Intermediate layer

13 Stratified skin/ife Envelope proteins Loricrin Involucrin Fillagrin Keratin 1/10 Keratin 5/14 Junctions: integrins Regeneration, skin types

14 Stratified skin/ife Thick skin Thin skin

15 Epidermal Appendages Surface ectoderm - Hair follicles, - Glands: sebaceous, sweat, apocrine, mammary, salivary, lacrimal - Nails - Teeth Share common developmental mechanisms: Epithelial to mesenchymal signaling inducing formation of placode and mesenchymal condensations, invagination of epidermis into dermis.

16 Hair follicle development and cycling Epidermal appendage Involved in thermoregulation/sun protection Permanent Infundibulum Cycling Month 2-4: Onset hair follicle development Hair follicles develop first in cranial region Month 5: most hair follicles present 5,000,000 hair follicles Anatomy

17 Hair follicle development Month 2 Birth: 5000,000 Mesenchymal condensate Dermal papilla Signaling events

18 Hair follicle development Hair germ Hair peg Bulbous hair peg Invasion of dermal cells

19 Hair follicle development Formation of: Arrector pili muscle Hair follicle bulge Germinal matrix Inner and outer root sheaths Babies are born with first generation of fine un-pigmented hairs: lanugo Postnatal regeneration: Hair follicle cycling Permanent Cycling

20 Postnatal hair follicle cycling germ peg bulbous peg Telogen: rest Anagen: growth Catagen: regression Ageing

21 Epidermal gland development Epidermal appendages: outgrowths from IFE or HF Sebaceous glands: sebrum/vernix Sweat glands Apocrine glands (pheromones) Mammary glands Salivary glands Lacrimal glands

22 Epidermal gland development Epidermal appendages Sebaceous glands: develop from hair follicle (4 weeks +) Sweat glands: develop from basal layer IFE (20 weeks+) Apocrine glands: develop in association with HFs, most lost late in fetal dev.

23 Mammary gland development Epidermal appendage 4 weeks: Postnatal regenerative growth

24 Teeth

25 Tooth development Ectoderm/cranial neural crest derived mesenchyme enamel dentin Week 6: dental lamina U-shaped ridge Week 7: Mesenchyme condensation Tucker and Sharpe, Nature Genetics 2004 Week 8: Mesenchyme invades base tooth bud: Dental papilla Week 14: Epithelial cells: Ameloblasts: enamel Mesenchymal cells: Odontoblasts: dentin

26 Week 6: dental lamina forms Tooth development Week 7-8: formation of tooth buds: Bud stage Week 8: formation of dental papilla: Cap and Bell Stage

27 Tooth development Primary teeth Adult teeth

28 Nails

29 Nail development Ectoderm Week 10: epidermal thickening, nail field Week 11: nail anlagen moves proximally, nail folds, proximal hair fold: formation of formative zone

30 Nail development Ectoderm

31 Melanocytes

32 Melanocyte development Neural crest Week 6 Ernfors, Exp Cell Res 2010

33 Melanocyte development Neural crest Week 6/7 Week 10 Active Proliferation Migration into epidermis Migration into Hair Pegs Final destination: Bulge Matrix Basal layer (Humans) Millar, Plos Biology 2005

34 Melanocyte development Neural crest Before stratification Onset stratification Bulbous hair pegs Anagen Matrix Hair follicle Bulge Djian-Zaouche, Pigment Cell Melanoma Res 2012

35 Dermis Connective tissue with: Fibroblasts Blood vessels Nerve endings Sensory receptors Muscle bundles

36 Dermis development Somitic mesoderm -> trunk Somatic lateral plate mesoderm -> trunk, limbs Cranial neural crest derived mesenchyme -> cranial region

37 Dermis development 3 Months: formation of papillary layer (dermal papillae and epidermal ridges) Inner dermis: reticular layer

38 Lecture overview Skin Skin origins Development of the overlying epidermis Development of epidermal appendages: Hair follicles Glands Mammary glands Nails Teeth Development of Melanocytes Development of the Dermis Resources: Larsen s Human Embryology Chapter 7 The Developing Human: Clinically Oriented Embryology Dr Annemiek Beverdam School of Medical Sciences, UNSW Wallace Wurth Building Room 234

39 QUIZ

40 1. Hair follicles develop from: A the epidermis B the dermis C the hypodermis D the melanocytes

41 1. Hair follicles develop from: A the epidermis B the dermis C the hypodermis D the melanocytes

42 2. Hair follicle development: A is controlled by signaling exclusively from the mesenchyme B is controlled by signaling exclusively from the surface ectoderm C is controlled by signaling from mesenchyme and surface ectoderm D is controlled by signaling from the melanocyte stem cells

43 2. Hair follicle development: A is controlled by signaling exclusively from the mesenchyme B is controlled by signaling exclusively from the surface ectoderm C is controlled by signaling from mesenchyme and surface ectoderm D is controlled by signaling from the melanocyte stem cells

44 3. The non-cranial dermis is derived from: A ectoderm B mesoderm C neurectoderm D endoderm

45 3. The non-cranial dermis is derived from: A ectoderm B mesoderm C neurectoderm D endoderm

46 4. Human melanocytes: A are ectodermal in origin B initially populate the dermis C are eventually localized in the basal epidermal layer and hair follicle D all of the above

47 4. Human melanocytes: A are ectodermal in origin B initially populate the dermis C are eventually localized in the basal epidermal layer and hair follicle D all of the above

48 5. Epidermal appendages are: A nails B mammary glands C teeth D all of the above

49 5. Epidermal appendages are: A nails B mammary glands C teeth D all of the above

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